Case Presentation:
- History: A 45 year old man has had a high fever for the past two days. During that time he has had a cough and has been bringing up more sputum, which has a thick, yellow appearance. On physical examination his vital signs are: T 38.5 C, P 90, RR 20, BP 115/75 mm Hg. Auscultation of the chest reveals bilateral crackles at both lung bases. There is dullness to percussion. A chest radiograph shows bilateral patchy infiltrates, mainly in lower lung fields. A CBC shows: WBC count 13,320/microliter, Hgb 13.9 g/dL, Hct 41.8%, MCV 85 fL, platelet count 317,500/microliter, and WBC differential count 78 segs, 8 bands, 8 lymphs, and 6 monos.
- What is this process?
- Pneumonia
- What type of infectious agent is most likely to be the cause?
- Bacteria.
- What findings are characteristic for this kind of infection?
- Illness of short duration, fever, cough productive of sputum, purulent sputum, high WBC count with left shift, patchy infiltrates.
- What are initial barriers to infection?
- There is an epithelial barrier to infection. An intact epithelium is the major defense against attack by infectious agents. The epithelium can produce peptides that have antibacterial properties.
- In the respiratory tract, the cough reflex helps to remove mucus and trapped organisms. The mucociliary apparatus helps to bring up inhaled organisms trapped in the mucus secreted into the airways. Mucus-secreting glands extend down to the level of the terminal bronchioles.
- What are initial cellular immune responses?
- An initial basic mechanism of the body's immune defenses is the recognition of the presence of microbial agents through receptor recognition. Cells of the innate immune system can utilize pattern recognition of non-self substances such as lipopolysaccharide, mannose residues, etc that are typical for bacteria, but not host cells.
- The initial response to infection can be mediated by:
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Intraepithelial T lymphocytes
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Neutrophils (Microscopic view of alveolar exudate with neutrophils)
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Macrophages (derived from blood monocytes)
- What are initial responses via circulating blood proteins?
- Proteins known as complement are circulating in the bloodstream. The complement system can become activated by infection, with binding of complement components to the organisms. With complement activation, several different complement components are used and are generated. There is sequential activation and production of proteolytic enzymes. Complement can be activated by any of three mechanisms:
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Alternate pathway - activation by microbial surface proteins
Animation: alternate pathway of complement activation
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Classic pathway - activation by immunoglobulin bound to microbial agents
Animation: classic pathway of complement activation
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Lectin pathway - mannose-binding lectin attaches to microbial glycoproteins and activates the classic pathway.
- The different components of complement activation have various functions:
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The C3b component coats microbial agents and enhances phagocytosis because of C3b receptors present on phagocytic cells.
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C5a component is a chemoattractant for neutrophils.
Animation: Neutrophil attraction
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"Membrane attack complex" (C5-9) punches holes in microbial cells.
- Describe the functions of the various cells involved in initial immune responses.
- Circulating granulocytes, mainly neutrophils (called polymorphonuclear leukocytes, or PMNs) respond to stimuli and migrate toward the source of the stimuli - chemoattractants cause migration of neutrophils outside of the bloodstream into the tissues that are infected. PMNs exhibit phagocytosis and killing of the micro-organisms with reactive oxygen intermediates.
Animation: phagocytosis of an infectious agent by a neutrophil
- Macrophages are derived from circulating blood monocytes. They can be attracted to areas of infectiion. Upon leaving the bloodstream, monocytes migrate into the tissues where they can engulf microbes as well as secrete a variety of cytokines, including interleukins:
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interleukin-12 to activate NK cells
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interleukin 1 to activate endothelial cells to become leaky in the inflammatory process
- Macrophages, through phagocytosis, can kill ingested microbes with nitric oxide.
- Macrophages secrete tumor necrosis factor (TNF) to activate neutrophils and produce inflammation
- NK cells (10% of circulating lymphocytes) recognize infected cells and lyse them. NK cells secrete gamma-interferon to activate macrophages. NK cells have Fc receptors on their surface to recognize cells that have become coated with immunoglobulin. NK cell granules are then released that have proteins which punch holes in plasma membranes of the infected cells and have proteins that turn on apoptotic mechanisms. NK cells have surface receptors to recognize class I MHC molecules and turn off NK activity in the presence of normal nucleated cells of the body.
Animation: the interaction of a macrophage (an antigen presenting cell) with an NK cell
- The by-product molecules of the innate immune response act as costimulators (adjuvants) for the adaptive immune responses.
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